Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19.     

Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Pharmacokinetics of a valpromide isomer,valnoctamide, in healthy subjects

Summary The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a prodrug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.     

筛检对肝癌死亡率影响的研究

5581名HBsAg阳性的男性随机分入周期性筛检组(A组,3712人)及对照组(B组,1869人)。A组(19155.4人年)共发生肝癌257例,B组(9785.5人年)为117例,两组的肝癌发生率分别为1342/10万与1196/10万;两组肝癌死亡分别为218与109例,肝癌死亡率分别为1138/10万与1114/10万。两组中Ⅰ期肝癌病例分别为29.6％与6.0％,差异有非常显著性意义。1、3、5年相对生存率A组为23.7％、7.0％、4.0％,B组为9.7％、4.0％、4.1％。用Poisson回归模型拟合显示,在调正年龄、初筛AFP及入列年份后,筛检对于肝癌的相对危险度为0.83,95％CI为0.68～1.03,有较弱的“保护”作用,Cox回归模型拟合结果显示当临床分期未引入模型时,筛检对于肝癌有显著的“保护”作用:危险率为0.6617,95％CI为0.5234～0.8365;而模型经调整后,危险率即接近“1”,95％CI为0.74～1.26。     

Cytologic diagnosis of non-oxyphil follicular neoplasias of the thyroid. Multivariate classification procedure based on quantitative nucleolar features.

The study was done on cytologic material of 58 non-oxyphil follicular neoplasias of the thyroid, 32 of which were adenomas and 26 carcinomas. Three groups of nucleolar features were quantified using a routine microscope with an ocular micrometer: frequency-, size-, and margination-related features. Since value overlap was present between two categories for all the variables, stepwise discriminant analysis was applied. The following three features were selected by the computer for calculation of one canonical discriminant function: percentage of marginated nucleoli, percentage of nuclei with one nucleolus, mean major nucleolar diameter. The percentage of agreement between morphologic and computer classifications was 95%. Two follicular adenomas were allocated to the carcinoma category, whereas one follicular carcinoma was allocated to the adenoma category. Out of 58, 52 were diagnosed by the computer into one of the two diagnostic categories with a very high probability, i.e. P greater than 0.75, the remaining 6 being considered intermediate.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.     

La «coxa pedis»

Résumé: La ?coxa pedis? correspond à l'?articulation talo-calcanéo-navicularis?. Structurée comme une énarthrose, il est possible de lui définir une épiphyse représentée par la tête et le col du talus et une cotyle structurée comme une cavité ostéo-fibro-cartilagineuse, à la constitution de laquelle concourent, comme éléments squelettiques, la surface articulaire postérieure du naviculaire et les surfaces articulaires des petites (sustentaculum tali) et grandes apophyses du calcanéus qui forment l'articulation sous-talienne antérieure; parfois divisées entre elles par un sillon, le plus souvent elles constituent une seule formation articulaire. La surface articulaire comprise entre le naviculaire, le sustentaculum tali et la grande apophyse du calcanéus est complétée par un fibro-cartilage gléno?dien renforcé superficiellement par le ligament calcanéo-naviculaire plantaire qui, prenant naissance à la base et sur le contour antéromédial du sustentaculum tali, s'insère distalement sur le tubercule et le bord inféro-postérieur du naviculaire. Ce ligament correspond au fond de la coxa pedis et sous-tend une véritable gléno?de, revêtue de cartilage, en relation articulaire avec le versant inféro-médial de la tête du talus compris entre les versants du naviculaire et du calcaneus. De plus, la présence de corpuscules proprioceptifs dans le ligament calcanéo-naviculaire plantaire fait penser à une fonction réceptrice cybernétique également de la coxa pedis. Aux stades foetaux précoces (16^e-17^e semaine), les articulations talo-naviculaire et sous-talienne antérieure sont différenciées dans une unique structure articulaire présentant des caractéristiques morphologiques d'énarthrose. Dans un sens plus ample, ?coxa pedis? peut définir la signification fonctionnelle particulière d'une structure qui, de par ses données anatomiques, évolutives et cliniques, peut être analogiquement comparée à l'articulation coxo-fémorale avec laquelle, ainsi qu'avec le genou, elle s'intègre fonctionnellement dans la structure plus complexe du membre inférieur. La différenciation énarthrosique proximale et distale au membre inférieur, avec le joint interposé représenté par le genou, est une prémisse biomécanique aux mécanismes de rotation (plan orthogonal aux axes segmentaires du membre) indispensables pour amorcer la stabilisation du membre dans la phase portante (cha?ne cinétique fermée); et, à la succession des mécanismes intercurrents dans le plan frontal (translation latérale de la charge lors du démarrage de la phase portante) et dans le plan sagittal (phase oscillante). Une référence particulière est faite à la pathologie gléno?dienne dégénérative et au syndrome de déstabilisation péritalienne. Récemment, une référence à la ?coxa pedis? (1999) a été faite dans l'édition mise à jour de l'Encyclopédie Médico-Chirurgicale rédigée par Biga, Moulies et Mabit.